In mature human and mouse pancreatic islets, B-cells are found in diploid and polyploid (predominantly tetraploid) states, while other cell types remain diploid. In 12-week-old diabetic mice (db/db) an octaploid class of B-cells appears, in contrast to normal controls which show only the two basic classes. In humans, polyploidy is limited to the endocrine pancreatic tissue, while in mice exocrine cells exhibit the same polyploid classes. In diabetic mice, the exocrine tissue shows a ploidy response parallel to that of the endocrine tissue. This project is proposed to characterize more fully the development of polyploid B-cells in normal and diabetic mouse islets, in terms of known stages of differentiation. Exocrine tissue of control and experimental animals will also be monitored. A qualitative evaluation of the polyploidy will first be made by cytophotometry on Feulgen-stained tissue to determine the relationship between DNA content and nuclear volume. If, as has been found consistently in the past, there is a rigid correlation between polyploidy and volume, semiautomatic particle size analysis using the Zeiss Particle Size Analyzer will be performed on either photographs or drawings of aldehyde-fuchsin or Feulgen-stained nuclei to determine percentages of cells in the various polyploid classes on relatively large populations of cells. This characterization will provide a base for further investigation of the role of polyploidization in the normal differentiation of the pancreas and its possible role in diabetes.